Knowledge of the dopamine (DA) neural systems arising from the ventral tegmentum appears to be crucial for a comprehensive understanding of the antipsychotic actions and motor side effects of neuroleptic drugs and may well be important in the etiology of major affectve disorders. Behavioral and biochemical studies in the rat have demonstrated that the steroid hormone, estrogen, can modulate midbrain DA function, and this implies that estrogenic compounds may have a significant role in mood disorders and certain aspects of mental function. Recent behavioral work in our laboratory has shown that estradiol benzoate (EB) can have very short-term (minutes) as well as prolonged (days) effects on the hyperactivity induced in rats by amphetamine (a DA agonist) or by a novel environment. The degree and even the direction of these effects varies according to the time interval between EB administration and activity testing. The electrophysiological project proposed here seeks to evaluate changes in DA post-synaptic function at various times after the administration of EB or oil using single unit recording within the nucleus accumbens; a terminal region believed to play a key role in the dopaminergic influence on locomoter activity. DA transmission will be measured by the effects of iontophoretically applied DA, of an iontophoretically applied DA receptor blocker, and by responses to synaptically released DA. These latter responses will be evoked by electrical stimulation of DA neuron cell bodies in the ventral tegmentum. Changes in basal levels of neural firing as well as in dopaminergically-induced effects after EB administration will be monitored as follows: (1) spontaneous and glutamate-enhanced unit firing patterns and rates, (2) responses evoked by electrical stimulation of afferents from the amygdala and (3) responses to sensory stimulation (somatic, olfactory). It is hoped that the findings of the proposed study will contribute towards the long-range goals of characterizing the interactions between hormones and midbrain DA systems using behavioral and neurophysiological techniques. The experience gained with this limited protocol will facilitate future studies in which these techniques are applied to other drugs when modes of action are important in psychiatry.